I'm fairly sure people will commute to the complete opposite side of your map if they want to. My biggest city is right under 200k people and sometimes I get bored and use the Follow thing just to see what they do. Those little buggers drive like maniacs on the curves.
Also, on the Districts subject. You can make any area, ANYWHERE a certain type of industry. The catch is that if the location does not have the natural resource, then it will have to import whatever it needs to produce things.
There was also that map where someone made a city with practically no cars by using a ton of ped walkways. They have no issue walking for miles either.